Using recombinant DNA techniques, a number of partially homologous D. melanogaster sequences have been isolated which are localized to the chromosome termini, or telomeres; the telomere region is necessay for chromosome stability and for the association of nonhomologous chromosome ends in interphase and meiotic prophase. The initial objective of the proposed studies is to determine whether the behavior of these terminally localized DNA sequences is correlated with the known behavior of telomeres. A number of cytogenetic experiments will determine whether the temporary association of nonhomologous chromosome ends is due to the presence of these terminal DNA sequences. Terminal DNA sequences involved in chromosome healing and stabilization will be isolated from the ends of a number of stable X chromosome terminal deletions; this approach depends upon a recently available method for isolating DNA fragments from specific regions of the D. melanogaster genome. It is also necessary to ascertain whether telomeric structural determinants can stably occur elsewhere in the genome; this approach depends upon a molecular and cytogenetic anslysis of many (25) cloned segments of D. melanogaster DNA which are homologous to the original cloned telomere probe. Do alterations in telomere structure result in the karyotypic abnormalities associated with neoplastic growth and the in vitro culture of cells? The karyotype and the molecular organization of telomeric sequences will be examined in Drosophila malignant neoplasms and cultured cells. Use will be made of a variety of different repair and recombination defective mutants of D. melanogaster in order to ascertain whether chromatid interchanges are responsible for the rapid evolution of DNA sequences at the telomere regions. The possible presence of telomere-specific DNA binding proteins will also be examined. In contrast to the telomeric DNA sequences which are essential for stable chromosome structure, there are highly mobile dispersed repeated genes in Drosophila which have an unstable organization in the genome. The cytogenetic organization of dispersed repeated genes will be examined in natural populations of D. melanogaster, since nothing is presently known about the behavior and stability of these elements outside of the laboratory.